Although almost 400,000 patients suffer cardiac arrest each year in the United States, average survival rates following Cardiopulmonary Resuscitation (CPR) have averaged <5% for the last 5 decades. Regrettably, manual standard CPR is inherently inefficient. Recent efforts have been shifted to reduce the ischemic damage to the brain and heart by increasing circulation with mechanical adjuncts and post arrest therapeutic hypothermia (TH). A method which promotes normalization of vital organ blood flow and simultaneously allows for intra-CPR TH could have the greatest impact on neurologically intact survival in cardiac arrest since the first description of chest compressions 50 years ago. In our grant proposal we describe the first favorable results and suggest research that needs to be performed on a new method of CPR with the potential to be used in all patients with cardiac arrest and maintain heart and brain viability for prolonged periods regardless of the presenting rhythm. We hypothesize that by using a combination of sodium nitroprusside (SNP), a potent vasodilator, and mechanical CPR adjuncts we can effectively normalize CPR-generated blood flow to the heart and brain. We further hypothesize that the pharmacologically induced cutaneous vasodilatation, combined with high forward blood flow, will facilitate intra- CPR heat exchange and TH. Our pilot data indicate that an achievable goal of this proposal is to conclusively show that elimination of thoracic and cerebral vasoconstriction with a potent vasodilator combined with non- invasive mechanical adjuncts that promote cardiac output and increase sub-diaphragmatic vascular resistance, will normalize and maintain vital organ perfusion during CPR. The pharmacological cutaneous vasodilatation will expedite heat exchange with surface cooling so that clinically valuable TH can be achieved before return to spontaneous circulation. Our proposed research will: 1.) identify the optimal combination of mechanical adjuncts and the optimal dose of sodium nitroprusside (SNP) to optimize flow and survival after cardiac arrest, 2.) demonstrate that SNP CPR offers similar benefits in different cardiac arrest models, and 3.) demonstrate that SNP CPR can provide immediate and effective intra-CPR therapeutic hypothermia. PUBLIC HEALTH RELEVANCE: Due to inherent ineffectiveness of standard CPR a new more efficient method is needed to significantly improve resuscitation outcomes and long term neurological intact survival. We propose a new method which includes a potent arterial dilator (sodium nitroprusside or SNP) and non invasive mechanical adjuncts that increase cardiac output and re-direct flow to the heart and brain. The proposed combination can efficiently be used for initiation of therapeutic hypothermia during CPR and preliminary studies have demonstrated a distinctive advantage compared to standard CPR in all resuscitation related outcomes.